Background: Prostaglandins are a family of eicosanoids biosynthesized from arachidonic acid through cyclooxygenase (COX) pathway. Two isoforms of COX are well established: COX-1, COX-2. Evidence supports the notion that cyclooxygenase-2, plays a crucial role in some pathological conditions such as inflammation and cancer.

Objective: A new group of 1,3-diphenyl-3-(phenylamino)propan-1-ones was designed and synthesized to investigate for their COX-2 inhibitory activity and inhibition of platelet aggregation.

Method: Docking study was performed using AutoDock vina software. In vitro COX-1 and COX- 2 isozyme inhibition studies were accomplished to obtain structure activity relationship data. The in vitro antiplatelet aggregation activity was determined by turbidimetric procedure.

Results: In vitro COX inhibition assay showed that except compound 8c, all derivatives were selective COX-2 inhibitors with IC50 values in the potent 0.20-0.35 µM range with high COX-2 selectivity indexes (SI). Molecular modeling and docking studies indicated that synthesized compounds had a binding similar to that of the known inhibitor SC-558 and the SO2Me group was inserted into the COX-2 secondary pocket (Val523, Phe518, Ile517, Arg513 and His90) and C=O of the central α, β-unsaturated-carbonyl moiety was oriented toward the entrance to the COX-2 binding site (Tyr355 and Arg120).

Conclusion: The 1,3-diphenyl-3-(phenylamino)propan-1-ones are novel COX-2 inhibitors with good COX-2 inhibitory and low affinity for COX-1 isoenzyme. Also our results demonstrated that majority of these compounds inhibited AA-induced platelet aggregation.

背景：前列腺素是花生四烯酸通过环氧合酶（COX）途径生物合成的类花生酸家族。很好地建立了两种COX异构体：COX-1，COX-2。有证据支持环氧合酶2在某些病理状况（例如炎症和癌症）中起关键作用的观点。

目的：设计合成一组新的1,3-二苯基-3-（苯氨基）丙烷-1-酮，研究其对COX-2的抑制活性和对血小板聚集的抑制作用。

方法：使用AutoDock vina软件进行对接研究。进行体外COX-1和COX-2同工酶抑制研究以获得结构活性关系数据。通过比浊法确定体外抗血小板聚集活性。

结果：体外COX抑制试验表明，除化合物8c外，所有衍生物均为选择性COX-2抑制剂，IC50值在0.20-0.35 µM的有效范围内，并具有较高的COX-2选择性指数（SI）。分子建模和对接研究表明，合成的化合物具有与已知抑制剂SC-558相似的结合力，并且SO2Me基团插入了COX-2二级口袋（Val523，Phe518，Ile517，Arg513和His90），C = O中心α，β-不饱和羰基部分的“α”朝向COX-2结合位点（Tyr355和Arg120）的入口。

结论：1,3-二苯基-3-（苯氨基）丙烷-1-酮是新型的COX-2抑制剂，对COX-1同工酶具有良好的COX-2抑制作用和低亲和力。我们的结果还表明，这些化合物中的大多数抑制了AA诱导的血小板凝集。